title: Synthesis and crystallographic study of 1,25-dihydroxyergocalciferol analogs.
abstract: The hybrid analogs of 1,25-dihydroxyergocalciferol (PRI-5201 and PRI-5202) were synthesized as potential anticancer agents using a convergent strategy. The analogs were designed by combining a 19-nor modification of the A-ring with the homologated and rigidified ergocalciferol-like side-chain of the previously obtained analogs PRI-1906 and PRI-1907. The strategy also allowed the novel efficient synthesis of 19-nor-1,25-dihydroxyergocalciferol (paricalcitol, PRI-5100) and its (24R)-diastereomer (PRI-5101). The single crystal X-ray structures of the 19-nor analogs (PRI-5100 and PRI-5101) were solved and refined. The A-ring of both analogs adopts exclusively chair β-conformation in the solid state. The side-chain of these analogs is coplanar with the CD-ring plane, while it is perpendicular in 1,25-dihydroxycholecalciferol.
authors.affiliation: Pharmaceutical Research Institute, 01-793 Warszawa, Poland. a.pietraszek@ifarm.eu
authors.forename: Anita
authors.initials: A
authors.lastname: Pietraszek
authors.forename: Maura
authors.initials: M
authors.lastname: Malińska
authors.forename: Michał
authors.initials: M
authors.lastname: Chodyński
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krupa
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Krajewski
authors.forename: Piotr
authors.initials: P
authors.lastname: Cmoch
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Woźniak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D004872:Ergocalciferols / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction
chemical_list: D000970:Antineoplastic Agents; D004872:Ergocalciferols
keywords: 19-nor vitamin D analogs; A-ring synthon; CD-ring fragment; Convergent synthesis; Paricalcitol; Single crystal X-ray structure